JUXTAPID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for JUXTAPID (JUXTAPID).

How it works

Microsomal triglyceride transfer protein (MTP) inhibitor; inhibits the assembly and secretion of apolipoprotein B-containing lipoproteins in the liver and intestine, thereby reducing plasma levels of LDL-C, total cholesterol, and triglycerides.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also by amide hydrolysis and glucuronidation.
Excretion	Primarily metabolized by CYP3A4 and to a minor extent by CYP3A5; less than 1% excreted unchanged in urine; approximately 4% excreted unchanged in feces; elimination is mainly via metabolism, with metabolites excreted in bile and feces.
Half-life	Terminal elimination half-life is approximately 60 hours, supporting once-daily dosing; steady-state is achieved within 2–3 weeks.
Protein binding	≥99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is approximately 1600 L (not standardized to weight; clinically indicates extensive tissue distribution).
Bioavailability	Absolute oral bioavailability is approximately 50% under fed conditions; bioavailability is significantly reduced (by 40%) when taken with low-fat meals.
Onset of Action	The clinical effect on LDL-C reduction is observed within 2 weeks of oral administration.
Duration of Action	After discontinuation, LDL-C returns to baseline within 4–6 weeks; once-daily dosing maintains effect over 24 hours.

Classification & Brands

Dosing & administration

60 mg orally once daily; may increase to 80 mg once daily if tolerated and LDL-C reduction is inadequate after 4 weeks.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in patients with severe renal impairment (CrCl <30 mL/min) due to lack of data.
Liver impairment	Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B or C). Use with caution in mild hepatic impairment (Child-Pugh class A); no specific dose adjustment provided but monitor for adverse effects.
Pediatric use	Safety and efficacy have not been established in pediatric patients; use is not recommended.
Geriatric use	No specific dose adjustments recommended based on age alone. Use with caution due to increased risk of adverse effects (e.g., hepatotoxicity, myopathy) and age-related comorbidities. Monitor liver function and creatine kinase regularly.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for JUXTAPID (JUXTAPID).

Breastfeeding	No data on presence in human milk. Lomitapide is lipophilic and may concentrate in breast milk; due to potential for serious adverse reactions in nursing infants (e.g., fat malabsorption), breastfeeding is not recommended during therapy and for 1 week after last dose. M/P ratio unknown.
Teratogenic Risk	Juxtapid (lomitapide) is contraindicated in pregnancy. Based on its mechanism of action (inhibition of microsomal triglyceride transfer protein), it is expected to cause fetal harm due to interference with fat absorption and essential fatty acid deficiency. No adequate human studies exist; animal studies show embryotoxicity and teratogenicity. Use is contraindicated during all trimesters.

Warnings & precautions

■ FDA Black Box Warning

Hepatotoxicity: Can cause elevations in serum transaminases and hepatic steatosis. Measure ALT and AST before and during therapy; dose reduce or discontinue if abnormalities occur.

Side Effect Profile

Serious Effects

Absolute Contraindications

Moderate or severe hepatic impairment (Child-Pugh class B or C), active liver disease including unexplained persistent elevations of serum transaminases, pregnancy, breastfeeding.

Clinical Precautions

Precautions

Hepatotoxicity, hepatic steatosis, risk of gastrointestinal adverse events (e.g., diarrhea, nausea), risk of malabsorption of fat-soluble vitamins and nutrients, bleeding risk due to decreased vitamin K levels.

Clinical Tips & Counseling

Drug interactions

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JUXTAPID

Clinical safety rating: caution

Comprehensive clinical and safety monograph for JUXTAPID (JUXTAPID).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also by amide hydrolysis and glucuronidation.
Excretion	Primarily metabolized by CYP3A4 and to a minor extent by CYP3A5; less than 1% excreted unchanged in urine; approximately 4% excreted unchanged in feces; elimination is mainly via metabolism, with metabolites excreted in bile and feces.
Half-life	Terminal elimination half-life is approximately 60 hours, supporting once-daily dosing; steady-state is achieved within 2–3 weeks.
Protein binding	≥99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is approximately 1600 L (not standardized to weight; clinically indicates extensive tissue distribution).
Bioavailability	Absolute oral bioavailability is approximately 50% under fed conditions; bioavailability is significantly reduced (by 40%) when taken with low-fat meals.
Onset of Action	The clinical effect on LDL-C reduction is observed within 2 weeks of oral administration.
Duration of Action	After discontinuation, LDL-C returns to baseline within 4–6 weeks; once-daily dosing maintains effect over 24 hours.

Classification & Brands

Dosing & administration

60 mg orally once daily; may increase to 80 mg once daily if tolerated and LDL-C reduction is inadequate after 4 weeks.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in patients with severe renal impairment (CrCl <30 mL/min) due to lack of data.
Liver impairment	Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B or C). Use with caution in mild hepatic impairment (Child-Pugh class A); no specific dose adjustment provided but monitor for adverse effects.
Pediatric use	Safety and efficacy have not been established in pediatric patients; use is not recommended.
Geriatric use	No specific dose adjustments recommended based on age alone. Use with caution due to increased risk of adverse effects (e.g., hepatotoxicity, myopathy) and age-related comorbidities. Monitor liver function and creatine kinase regularly.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for JUXTAPID (JUXTAPID).

Breastfeeding	No data on presence in human milk. Lomitapide is lipophilic and may concentrate in breast milk; due to potential for serious adverse reactions in nursing infants (e.g., fat malabsorption), breastfeeding is not recommended during therapy and for 1 week after last dose. M/P ratio unknown.
Teratogenic Risk	Juxtapid (lomitapide) is contraindicated in pregnancy. Based on its mechanism of action (inhibition of microsomal triglyceride transfer protein), it is expected to cause fetal harm due to interference with fat absorption and essential fatty acid deficiency. No adequate human studies exist; animal studies show embryotoxicity and teratogenicity. Use is contraindicated during all trimesters.

Warnings & precautions

■ FDA Black Box Warning

Hepatotoxicity: Can cause elevations in serum transaminases and hepatic steatosis. Measure ALT and AST before and during therapy; dose reduce or discontinue if abnormalities occur.

Side Effect Profile

Serious Effects

Absolute Contraindications

Moderate or severe hepatic impairment (Child-Pugh class B or C), active liver disease including unexplained persistent elevations of serum transaminases, pregnancy, breastfeeding.